Adenosine regulates a wide range of physiological functions through interaction with at least two major classes of adenosine receptors. The A1 and A3 classes of adenosine receptors are inhibitory to adenylate cyclase, while the A2 class is stimulatory to adenylate cyclase. Subclasses of adenosine receptors also occur. Some of these are inhibitory to calcium channels, some are stimulatory to potassium channels, some activate guanylate cyclase, some modulate phospholipid turn-over and some cause smooth muscle relaxation. Possible sites of action of caffeine and theophylline besides blockade of A1-, A2a- and A2b-adenosine receptors remain poorly defined. Inhibition of phosphodiesterase does not seem relevant to the behavioral stimulant activity of caffeine and theophylline since xanthines that are potent inhibitors of phosphodiesterases are behavioral depressants. Effects on GABA/A receptors may account for anxiogenic properties of caffeine, while a role for caffeine-elicited modulation of calcium-release from ryanodine-sensitive intracellular pools is unclear. The anxiolytic pyrazolopyridines, such as cartazolate, share with caffeine, actions at the following sites: i)adenosine receptors, ii) phosphodiesterases, iii) GABA/A-receptors, and iv) calcium release. A range of xanthines and of pyrazolopyridines are being investigated with respect to these different sites of action. Both are antagonists at adenosine receptors. The xanthines inhibit [3H]diazepam binding, while pyrazolopyridines have biphasic effects; stimulatory, and then at higher concentrations inhibitory. Chronic effects of xanthines/pyrazolopyridines on densities of central receptors and behavioral responses to different agents are also being compared. In a mast cell line, adenosine analogs appear to cause an IP3-dependent release of intracellular calcium through an A3-adenosine receptor. However, total accumulation of IP2 and IP1 appears only partly dependent on the A3-adenosine receptor-mediated pathway.